{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:37:30Z","timestamp":1791509850795,"version":"4.3.4"},"reference-count":66,"publisher":"National Academy of Sciences","issue":"5","license":[{"start":{"date-parts":[[2020,7,21]],"date-time":"2020-07-21T00:00:00Z","timestamp":1595289600000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Department of Health | National Health and Medical Research Council","doi-asserted-by":"publisher","award":["APP1161803"],"award-info":[{"award-number":["APP1161803"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000923","name":"Australian Research Council","doi-asserted-by":"publisher","award":["DP170103093"],"award-info":[{"award-number":["DP170103093"]}],"id":[{"id":"10.13039\/501100000923","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,2,4]]},"abstract":"<jats:p>\n                    The accumulation of protein deposits in neurodegenerative diseases has been hypothesized to depend on a metastable subproteome vulnerable to aggregation. To investigate this phenomenon and the mechanisms that regulate it, we measured the solubility of the proteome in the mouse Neuro2a cell line under six different protein homeostasis stresses: 1) Huntington\u2019s disease proteotoxicity, 2) Hsp70, 3) Hsp90, 4) proteasome, 5) endoplasmic reticulum (ER)-mediated folding inhibition, and 6) oxidative stress. Overall, we found that about one-fifth of the proteome changed solubility with almost all of the increases in insolubility were counteracted by increases in solubility of other proteins. Each stress directed a highly specific pattern of change, which reflected the remodeling of protein complexes involved in adaptation to perturbation, most notably, stress granule (SG) proteins, which responded differently to different stresses. These results indicate that the protein homeostasis system is organized in a modular manner and aggregation patterns were not correlated with protein folding stability (\u0394\n                    <jats:italic>G<\/jats:italic>\n                    ). Instead, distinct cellular mechanisms regulate assembly patterns of multiple classes of protein complexes under different stress conditions.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1912897117","type":"journal-article","created":{"date-parts":[[2020,1,21]],"date-time":"2020-01-21T17:55:47Z","timestamp":1579629347000},"page":"2422-2431","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":68,"title":["Widespread remodeling of proteome solubility in response to different protein homeostasis stresses"],"prefix":"10.1073","volume":"117","author":[{"given":"Xiaojing","family":"Sui","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas E. V.","family":"Pires","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia;"},{"name":"Centro de Pesquisas Ren\u00e9 Rachou, Funda\u00e7\u00e3o Oswaldo Cruz, Belo Horizonte, Minas Gerais 30.190-009, Brazil;"},{"name":"School of Computing and Information Systems, The University of Melbourne, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique R.","family":"Ormsby","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezerae","family":"Cox","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Nie","sequence":"additional","affiliation":[{"name":"Melbourne Mass Spectrometry and Proteomics Facility, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Vecchi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, CB2 1EW Cambridge, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3616-1610","authenticated-orcid":false,"given":"Michele","family":"Vendruscolo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Centre for Misfolding Diseases, University of Cambridge, CB2 1EW Cambridge, United Kingdom;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Ascher","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin E.","family":"Reid","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia;"},{"name":"School of Chemistry, The University of Melbourne, VIC 3010, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9965-2847","authenticated-orcid":false,"given":"Danny M.","family":"Hatters","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, VIC 3010, Australia;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,1,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"crossref","first-page":"3861","DOI":"10.1242\/jcs.173047","article-title":"Surviving protein quality control catastrophes\u2013From cells to organisms","volume":"128","author":"Schneider K.","year":"2015","unstructured":"K. Schneider, A. Bertolotti, Surviving protein quality control catastrophes\u2013From cells to organisms. J. Cell Sci. 128, 3861\u20133869 (2015).","journal-title":"J. Cell Sci."},{"key":"e_1_3_3_2_2","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1038\/nrm3810","article-title":"The amyloid state and its association with protein misfolding diseases","volume":"15","author":"Knowles T. P.","year":"2014","unstructured":"T. P. Knowles, M. Vendruscolo, C. M. Dobson, The amyloid state and its association with protein misfolding diseases. Nat. Rev. Mol. Cell Biol. 15, 384\u2013396 (2014).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"e_1_3_3_3_2","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.1172\/JCI24761","article-title":"The genetic epidemiology of neurodegenerative disease","volume":"115","author":"Bertram L.","year":"2005","unstructured":"L. Bertram, R. E. Tanzi, The genetic epidemiology of neurodegenerative disease. J. Clin. Invest. 115, 1449\u20131457 (2005).","journal-title":"J. Clin. Invest."},{"key":"e_1_3_3_4_2","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.tcb.2014.05.003","article-title":"Proteostasis impairment in protein-misfolding and -aggregation diseases","volume":"24","author":"Hipp M. S.","year":"2014","unstructured":"M. S. Hipp, S. H. Park, F. U. Hartl, Proteostasis impairment in protein-misfolding and -aggregation diseases. Trends Cell Biol. 24, 506\u2013514 (2014).","journal-title":"Trends Cell Biol."},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2018.05.003"},{"key":"e_1_3_3_6_2","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.cell.2013.06.003","article-title":"PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone","volume":"154","author":"Park S. H.","year":"2013","unstructured":"S. H. Park ., PolyQ proteins interfere with nuclear degradation of cytosolic proteins by sequestering the Sis1p chaperone. Cell 154, 134\u2013145 (2013).","journal-title":"Cell"},{"key":"e_1_3_3_7_2","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1126\/science.1124514","article-title":"Progressive disruption of cellular protein folding in models of polyglutamine diseases","volume":"311","author":"Gidalevitz T.","year":"2006","unstructured":"T. Gidalevitz, A. Ben-Zvi, K. H. Ho, H. R. Brignull, R. I. Morimoto, Progressive disruption of cellular protein folding in models of polyglutamine diseases. Science 311, 1471\u20131474 (2006).","journal-title":"Science"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"e1000399","DOI":"10.1371\/journal.pgen.1000399","article-title":"Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity","volume":"5","author":"Gidalevitz T.","year":"2009","unstructured":"T. Gidalevitz, T. Krupinski, S. Garcia, R. I. Morimoto, Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity. PLoS Genet. 5, e1000399 (2009).","journal-title":"PLoS Genet."},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.cell.2015.03.032","article-title":"Widespread proteome remodeling and aggregation in aging C. elegans","volume":"161","author":"Walther D. M.","year":"2015","unstructured":"D. M. Walther ., Widespread proteome remodeling and aggregation in aging C. elegans. Cell 161, 919\u2013932 (2015).","journal-title":"Cell"},{"key":"e_1_3_3_10_2","doi-asserted-by":"crossref","first-page":"1286","DOI":"10.1016\/j.cell.2015.08.041","article-title":"Reversible, specific, active aggregates of endogenous proteins assemble upon heat stress","volume":"162","author":"Wallace E. W.","year":"2015","unstructured":"E. W. Wallace ., Reversible, specific, active aggregates of endogenous proteins assemble upon heat stress. Cell 162, 1286\u20131298 (2015).","journal-title":"Cell"},{"key":"e_1_3_3_11_2","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/ng0893-387","article-title":"Trinucleotide repeat length instability and age of onset in huntington\u2019s disease","volume":"4","author":"Duyao M.","year":"1993","unstructured":"M. Duyao ., Trinucleotide repeat length instability and age of onset in huntington\u2019s disease. Nat. Genet. 4, 387\u2013392 (1993).","journal-title":"Nat. Genet."},{"key":"e_1_3_3_12_2","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1126\/science.277.5334.1990","article-title":"Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain","volume":"277","author":"DiFiglia M.","year":"1997","unstructured":"M. DiFiglia ., Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science 277, 1990\u20131993 (1997).","journal-title":"Science"},{"key":"e_1_3_3_13_2","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1038\/nature02998","article-title":"Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death","volume":"431","author":"Arrasate M.","year":"2004","unstructured":"M. Arrasate, S. Mitra, E. S. Schweitzer, M. R. Segal, S. Finkbeiner, Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Nature 431, 805\u2013810 (2004).","journal-title":"Nature"},{"key":"e_1_3_3_14_2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1016\/j.celrep.2017.04.029","article-title":"Huntingtin inclusions trigger cellular quiescence, deactivate apoptosis, and lead to delayed necrosis","volume":"19","author":"Ramdzan Y. M.","year":"2017","unstructured":"Y. M. Ramdzan ., Huntingtin inclusions trigger cellular quiescence, deactivate apoptosis, and lead to delayed necrosis. Cell Rep. 19, 919\u2013927 (2017).","journal-title":"Cell Rep."},{"key":"e_1_3_3_15_2","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1038\/nmeth.1930","article-title":"Tracking protein aggregation and mislocalization in cells with flow cytometry","volume":"9","author":"Ramdzan Y. M.","year":"2012","unstructured":"Y. M. Ramdzan ., Tracking protein aggregation and mislocalization in cells with flow cytometry. Nat. Methods 9, 467\u2013470 (2012).","journal-title":"Nat. Methods"},{"key":"e_1_3_3_16_2","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.molcel.2016.07.022","article-title":"Soluble oligomers of PolyQ-expanded huntingtin target a multiplicity of key cellular factors","volume":"63","author":"Kim Y. E.","year":"2016","unstructured":"Y. E. Kim ., Soluble oligomers of PolyQ-expanded huntingtin target a multiplicity of key cellular factors. Mol. Cell 63, 951\u2013964 (2016).","journal-title":"Mol. Cell"},{"key":"e_1_3_3_17_2","doi-asserted-by":"crossref","first-page":"35236","DOI":"10.1038\/srep35236","article-title":"FUS\/TLS acts as an aggregation-dependent modifier of polyglutamine disease model mice","volume":"6","author":"Kino Y.","year":"2016","unstructured":"Y. Kino ., FUS\/TLS acts as an aggregation-dependent modifier of polyglutamine disease model mice. Sci. Rep. 6, 35236 (2016).","journal-title":"Sci. Rep."},{"key":"e_1_3_3_18_2","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.4161\/cc.20423","article-title":"Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis","volume":"11","author":"Ratovitski T.","year":"2012","unstructured":"T. Ratovitski ., Huntingtin protein interactions altered by polyglutamine expansion as determined by quantitative proteomic analysis. Cell Cycle 11, 2006\u20132021 (2012).","journal-title":"Cell Cycle"},{"key":"e_1_3_3_19_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.neuron.2012.05.024","article-title":"Network organization of the huntingtin proteomic interactome in mammalian brain","volume":"75","author":"Shirasaki D. I.","year":"2012","unstructured":"D. I. Shirasaki ., Network organization of the huntingtin proteomic interactome in mammalian brain. Neuron 75, 41\u201357 (2012).","journal-title":"Neuron"},{"key":"e_1_3_3_20_2","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1016\/j.jmb.2018.03.031","article-title":"Tadpole-like conformations of huntingtin exon 1 are characterized by conformational heterogeneity that persists regardless of polyglutamine length","volume":"430","author":"Newcombe E. A.","year":"2018","unstructured":"E. A. Newcombe ., Tadpole-like conformations of huntingtin exon 1 are characterized by conformational heterogeneity that persists regardless of polyglutamine length. J. Mol. Biol. 430, 1442\u20131458 (2018).","journal-title":"J. Mol. Biol."},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/j.cell.2018.06.006","article-title":"A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins","volume":"174","author":"Wang J.","year":"2018","unstructured":"J. Wang ., A molecular grammar governing the driving forces for phase separation of prion-like RNA binding proteins. Cell 174, 688\u2013699 (2018).","journal-title":"Cell"},{"key":"e_1_3_3_22_2","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.cell.2017.12.032","article-title":"Context-dependent and disease-specific diversity in protein interactions within stress granules","volume":"172","author":"Markmiller S.","year":"2018","unstructured":"S. Markmiller ., Context-dependent and disease-specific diversity in protein interactions within stress granules. Cell 172, 590\u2013604 (2018).","journal-title":"Cell"},{"key":"e_1_3_3_23_2","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.cell.2015.12.038","article-title":"ATPase-modulated stress granules contain a diverse proteome and substructure","volume":"164","author":"Jain S.","year":"2016","unstructured":"S. Jain ., ATPase-modulated stress granules contain a diverse proteome and substructure. Cell 164, 487\u2013498 (2016).","journal-title":"Cell"},{"key":"e_1_3_3_24_2","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1016\/j.cell.2018.03.025","article-title":"Stress granule assembly disrupts nucleocytoplasmic transport","volume":"173","author":"Zhang K.","year":"2018","unstructured":"K. Zhang ., Stress granule assembly disrupts nucleocytoplasmic transport. Cell 173, 958\u2013971 (2018).","journal-title":"Cell"},{"key":"e_1_3_3_25_2","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.molcel.2018.02.004","article-title":"Ubiquitin modulates liquid-liquid phase separation of UBQLN2 via disruption of multivalent interactions","volume":"69","author":"Dao T. P.","year":"2018","unstructured":"T. P. Dao ., Ubiquitin modulates liquid-liquid phase separation of UBQLN2 via disruption of multivalent interactions. Mol. Cell 69, 965\u2013978 (2018).","journal-title":"Mol. Cell"},{"key":"e_1_3_3_26_2","doi-asserted-by":"crossref","first-page":"e9942","DOI":"10.1371\/journal.pone.0009942","article-title":"eIF5A promotes translation elongation, polysome disassembly and stress granule assembly","volume":"5","author":"Li C. H.","year":"2010","unstructured":"C. H. Li, T. Ohn, P. Ivanov, S. Tisdale, P. Anderson, eIF5A promotes translation elongation, polysome disassembly and stress granule assembly. PLoS One 5, e9942 (2010).","journal-title":"PLoS One"},{"key":"e_1_3_3_27_2","doi-asserted-by":"crossref","first-page":"1765","DOI":"10.1091\/mbc.e12-01-0040","article-title":"Perispeckles are major assembly sites for the exon junction core complex","volume":"23","author":"Daguenet E.","year":"2012","unstructured":"E. Daguenet ., Perispeckles are major assembly sites for the exon junction core complex. Mol. Biol. Cell 23, 1765\u20131782 (2012).","journal-title":"Mol. Biol. Cell"},{"key":"e_1_3_3_28_2","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.molcel.2017.02.013","article-title":"Phase separation of C9orf72 dipeptide repeats perturbs stress granule dynamics","volume":"65","author":"Boeynaems S.","year":"2017","unstructured":"S. Boeynaems ., Phase separation of C9orf72 dipeptide repeats perturbs stress granule dynamics. Mol. Cell 65, 1044\u20131055(2017).","journal-title":"Mol. Cell"},{"key":"e_1_3_3_29_2","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.neuron.2017.07.025","article-title":"TIA1 mutations in amyotrophic lateral sclerosis and frontotemporal dementia promote phase separation and alter stress granule dynamics","volume":"95","author":"Mackenzie I. R.","year":"2017","unstructured":"I. R. Mackenzie ., TIA1 mutations in amyotrophic lateral sclerosis and frontotemporal dementia promote phase separation and alter stress granule dynamics. Neuron 95, 808\u2013816 (2017).","journal-title":"Neuron"},{"key":"e_1_3_3_30_2","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.15252\/embj.201695957","article-title":"An aberrant phase transition of stress granules triggered by misfolded protein and prevented by chaperone function","volume":"36","author":"Mateju D.","year":"2017","unstructured":"D. Mateju ., An aberrant phase transition of stress granules triggered by misfolded protein and prevented by chaperone function. EMBO J. 36, 1669\u20131687 (2017).","journal-title":"EMBO J."},{"key":"e_1_3_3_31_2","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1016\/j.celrep.2017.10.097","article-title":"Spatiotemporal proteomic profiling of huntington\u2019s disease inclusions reveals widespread loss of protein function","volume":"21","author":"Hosp F.","year":"2017","unstructured":"F. Hosp ., Spatiotemporal proteomic profiling of huntington\u2019s disease inclusions reveals widespread loss of protein function. Cell Rep. 21, 2291\u20132303 (2017).","journal-title":"Cell Rep."},{"key":"e_1_3_3_32_2","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1038\/nrneurol.2017.99","article-title":"ER stress and the unfolded protein response in neurodegeneration","volume":"13","author":"Hetz C.","year":"2017","unstructured":"C. Hetz, S. Saxena, ER stress and the unfolded protein response in neurodegeneration. Nat. Rev. Neurol. 13, 477\u2013491 (2017).","journal-title":"Nat. Rev. Neurol."},{"key":"e_1_3_3_33_2","doi-asserted-by":"crossref","first-page":"252","DOI":"10.3390\/biom4010252","article-title":"Heavy metals and metalloids as a cause for protein misfolding and aggregation","volume":"4","author":"Tam\u00e1s M. J.","year":"2014","unstructured":"M. J. Tam\u00e1s, S. K. Sharma, S. Ibstedt, T. Jacobson, P. Christen, Heavy metals and metalloids as a cause for protein misfolding and aggregation. Biomolecules 4, 252\u2013267 (2014).","journal-title":"Biomolecules"},{"key":"e_1_3_3_34_2","first-page":"5073","article-title":"Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast","volume":"125","author":"Jacobson T.","year":"2012","unstructured":"T. Jacobson ., Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast. J. Cell Sci. 125, 5073\u20135083 (2012).","journal-title":"J. Cell Sci."},{"key":"e_1_3_3_35_2","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1083\/jcb.200803022","article-title":"Heat shock and oxygen radicals stimulate ubiquitin-dependent degradation mainly of newly synthesized proteins","volume":"182","author":"Medicherla B.","year":"2008","unstructured":"B. Medicherla, A. L. Goldberg, Heat shock and oxygen radicals stimulate ubiquitin-dependent degradation mainly of newly synthesized proteins. J. Cell Biol. 182, 663\u2013673 (2008).","journal-title":"J. Cell Biol."},{"key":"e_1_3_3_36_2","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1021\/jm801627a","article-title":"Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design","volume":"52","author":"Williamson D. S.","year":"2009","unstructured":"D. S. Williamson ., Novel adenosine-derived inhibitors of 70 kDa heat shock protein, discovered through structure-based design. J. Med. Chem. 52, 1510\u20131513 (2009).","journal-title":"J. Med. Chem."},{"key":"e_1_3_3_37_2","doi-asserted-by":"crossref","first-page":"e78443","DOI":"10.1371\/journal.pone.0078443","article-title":"Functional analysis of Hsp70 inhibitors","volume":"8","author":"Schlecht R.","year":"2013","unstructured":"R. Schlecht ., Functional analysis of Hsp70 inhibitors. PLoS One 8, e78443 (2013).","journal-title":"PLoS One"},{"key":"e_1_3_3_38_2","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41467-017-02562-5","article-title":"A biosensor-based framework to measure latent proteostasis capacity","volume":"9","author":"Wood R. J.","year":"2018","unstructured":"R. J. Wood ., A biosensor-based framework to measure latent proteostasis capacity. Nat. Commun. 9, 287 (2018).","journal-title":"Nat. Commun."},{"key":"e_1_3_3_39_2","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1083\/jcb.201210077","article-title":"Development of proteasome inhibitors as research tools and cancer drugs","volume":"199","author":"Goldberg A. L.","year":"2012","unstructured":"A. L. Goldberg, Development of proteasome inhibitors as research tools and cancer drugs. J. Cell Biol. 199, 583\u2013588 (2012).","journal-title":"J. Cell Biol."},{"key":"e_1_3_3_40_2","first-page":"a013177","article-title":"Protein-folding homeostasis in the endoplasmic reticulum and nutritional regulation","volume":"4","author":"Ron D.","year":"2012","unstructured":"D. Ron, H. P. Harding, Protein-folding homeostasis in the endoplasmic reticulum and nutritional regulation. Cold Spring Harb. Perspect. Biol. 4, a013177 (2012).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"e_1_3_3_41_2","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.redox.2012.11.010","article-title":"Arsenite-induced stress signaling: Modulation of the phosphoinositide 3\u2032-kinase\/Akt\/FoxO signaling cascade","volume":"1","author":"Hamann I.","year":"2013","unstructured":"I. Hamann, L. O. Klotz, Arsenite-induced stress signaling: Modulation of the phosphoinositide 3\u2032-kinase\/Akt\/FoxO signaling cascade. Redox Biol. 1, 104\u2013109 (2013).","journal-title":"Redox Biol."},{"key":"e_1_3_3_42_2","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.freeradbiomed.2011.04.008","article-title":"Arsenic-induced oxidative stress and its reversibility","volume":"51","author":"Flora S. J.","year":"2011","unstructured":"S. J. Flora, Arsenic-induced oxidative stress and its reversibility. Free Radic. Biol. Med. 51, 257\u2013281 (2011).","journal-title":"Free Radic. Biol. Med."},{"key":"e_1_3_3_43_2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/S0962-8924(00)01852-3","article-title":"Aggresomes, inclusion bodies and protein aggregation","volume":"10","author":"Kopito R. R.","year":"2000","unstructured":"R. R. Kopito, Aggresomes, inclusion bodies and protein aggregation. Trends Cell Biol. 10, 524\u2013530 (2000).","journal-title":"Trends Cell Biol."},{"key":"e_1_3_3_44_2","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.cell.2012.06.047","article-title":"Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition","volume":"150","author":"Taipale M.","year":"2012","unstructured":"M. Taipale ., Quantitative analysis of HSP90-client interactions reveals principles of substrate recognition. Cell 150, 987\u20131001 (2012).","journal-title":"Cell"},{"key":"e_1_3_3_45_2","doi-asserted-by":"crossref","first-page":"M111.014654","DOI":"10.1074\/mcp.M111.014654","article-title":"Quantitative proteomics reveals that Hsp90 inhibition preferentially targets kinases and the DNA damage response","volume":"11","author":"Sharma K.","year":"2012","unstructured":"K. Sharma ., Quantitative proteomics reveals that Hsp90 inhibition preferentially targets kinases and the DNA damage response. Mol Cell Proteomics 11, M111.014654 (2012).","journal-title":"Mol Cell Proteomics"},{"key":"e_1_3_3_46_2","doi-asserted-by":"crossref","first-page":"2702","DOI":"10.2174\/092986708786242895","article-title":"Novobiocin and additional inhibitors of the Hsp90 C-terminal nucleotide-binding pocket","volume":"15","author":"Donnelly A.","year":"2008","unstructured":"A. Donnelly, B. S. Blagg, Novobiocin and additional inhibitors of the Hsp90 C-terminal nucleotide-binding pocket. Curr. Med. Chem. 15, 2702\u20132717 (2008).","journal-title":"Curr. Med. Chem."},{"key":"e_1_3_3_47_2","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s002800050817","article-title":"The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin","volume":"42","author":"Schulte T. W.","year":"1998","unstructured":"T. W. Schulte, L. M. Neckers, The benzoquinone ansamycin 17-allylamino-17-demethoxygeldanamycin binds to HSP90 and shares important biologic activities with geldanamycin. Cancer Chemother. Pharmacol. 42, 273\u2013279 (1998).","journal-title":"Cancer Chemother. Pharmacol."},{"key":"e_1_3_3_48_2","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0092-8674(00)81588-3","article-title":"Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1","volume":"94","author":"Zou J.","year":"1998","unstructured":"J. Zou, Y. Guo, T. Guettouche, D. F. Smith, R. Voellmy, Repression of heat shock transcription factor HSF1 activation by HSP90 (HSP90 complex) that forms a stress-sensitive complex with HSF1. Cell 94, 471\u2013480 (1998).","journal-title":"Cell"},{"key":"e_1_3_3_49_2","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/j.bbabio.2011.08.010","article-title":"Understanding mitochondrial complex I assembly in health and disease","volume":"1817","author":"Mimaki M.","year":"2012","unstructured":"M. Mimaki, X. Wang, M. McKenzie, D. R. Thorburn, M. T. Ryan, Understanding mitochondrial complex I assembly in health and disease. Biochim. Biophys. Acta 1817, 851\u2013862 (2012).","journal-title":"Biochim. Biophys. Acta"},{"key":"e_1_3_3_50_2","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1126\/science.aad2033","article-title":"Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA","volume":"351","author":"Woerner A. C.","year":"2016","unstructured":"A. C. Woerner ., Cytoplasmic protein aggregates interfere with nucleocytoplasmic transport of protein and RNA. Science 351, 173\u2013176 (2016).","journal-title":"Science"},{"key":"e_1_3_3_51_2","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.neuron.2017.03.023","article-title":"Mutant huntingtin disrupts the nuclear pore complex","volume":"94","author":"Grima J. C.","year":"2017","unstructured":"J. C. Grima ., Mutant huntingtin disrupts the nuclear pore complex. Neuron 94, 93\u2013107 (2017).","journal-title":"Neuron"},{"key":"e_1_3_3_52_2","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.neuron.2018.07.039","article-title":"Tau protein disrupts nucleocytoplasmic transport in alzheimer\u2019s disease","volume":"99","author":"Eftekharzadeh B.","year":"2018","unstructured":"B. Eftekharzadeh ., Tau protein disrupts nucleocytoplasmic transport in alzheimer\u2019s disease. Neuron 99, 925\u2013940 (2018). Erratum in: Neuron 101, 349 (2019).","journal-title":"Neuron"},{"key":"e_1_3_3_53_2","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1038\/nature14974","article-title":"GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport","volume":"525","author":"Freibaum B. D.","year":"2015","unstructured":"B. D. Freibaum ., GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport. Nature 525, 129\u2013133 (2015).","journal-title":"Nature"},{"key":"e_1_3_3_54_2","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature14973","article-title":"The C9orf72 repeat expansion disrupts nucleocytoplasmic transport","volume":"525","author":"Zhang K.","year":"2015","unstructured":"K. Zhang ., The C9orf72 repeat expansion disrupts nucleocytoplasmic transport. Nature 525, 56\u201361 (2015).","journal-title":"Nature"},{"key":"e_1_3_3_55_2","first-page":"2247\u20132273","article-title":"The coming-of-age of nucleocytoplasmic transport in motor neuron disease and neurodegeneration","volume":"76","author":"Ferreira P. A.","year":"2019","unstructured":"P. A. Ferreira, The coming-of-age of nucleocytoplasmic transport in motor neuron disease and neurodegeneration. Cell. Mol. Life Sci. 76, 2247\u20132273 (2019). Erratum: Cell. Mol. Life Sci. 76, 2275 (2019).","journal-title":"Cell. Mol. Life Sci."},{"key":"e_1_3_3_56_2","doi-asserted-by":"crossref","first-page":"6081","DOI":"10.1073\/pnas.1819851116","article-title":"Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome","volume":"116","author":"Walker E. J.","year":"2019","unstructured":"E. J. Walker, J. Q. Bettinger, K. A. Welle, J. R. Hryhorenko, S. Ghaemmaghami, Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome. Proc. Natl. Acad. Sci. U.S.A. 116, 6081\u20136090 (2019).","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"e_1_3_3_57_2","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1126\/science.1134108","article-title":"Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis","volume":"314","author":"Neumann M.","year":"2006","unstructured":"M. Neumann ., Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Science 314, 130\u2013133 (2006).","journal-title":"Science"},{"key":"e_1_3_3_58_2","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nrn.2015.1","article-title":"Tau in physiology and pathology","volume":"17","author":"Wang Y.","year":"2016","unstructured":"Y. Wang, E. Mandelkow, Tau in physiology and pathology. Nat. Rev. Neurosci. 17, 5\u201321 (2016).","journal-title":"Nat. Rev. Neurosci."},{"key":"e_1_3_3_59_2","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s00401-018-1895-y","article-title":"Changes in proteome solubility indicate widespread proteostatic disruption in mouse models of neurodegenerative disease","volume":"136","author":"Pace M. C.","year":"2018","unstructured":"M. C. Pace ., Changes in proteome solubility indicate widespread proteostatic disruption in mouse models of neurodegenerative disease. Acta Neuropathol. 136, 919\u2013938 (2018).","journal-title":"Acta Neuropathol."},{"key":"e_1_3_3_60_2","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1017\/S1462399408000793","article-title":"Molecular pathology of myofibrillar myopathies","volume":"10","author":"Ferrer I.","year":"2008","unstructured":"I. Ferrer, M. Oliv\u00e9, Molecular pathology of myofibrillar myopathies. Expert Rev. Mol. Med. 10, e25 (2008).","journal-title":"Expert Rev. Mol. Med."},{"key":"e_1_3_3_61_2","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1242\/jcs.179887","article-title":"HSPB7 interacts with dimerized FLNC and its absence results in progressive myopathy in skeletal muscles","volume":"129","author":"Juo L. Y.","year":"2016","unstructured":"L. Y. Juo ., HSPB7 interacts with dimerized FLNC and its absence results in progressive myopathy in skeletal muscles. J. Cell Sci. 129, 1661\u20131670 (2016).","journal-title":"J. Cell Sci."},{"key":"e_1_3_3_62_2","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1097\/WCO.0000000000000357","article-title":"New aspects of myofibrillar myopathies","volume":"29","author":"Kley R. A.","year":"2016","unstructured":"R. A. Kley, M. Oliv\u00e9, R. Schr\u00f6der, New aspects of myofibrillar myopathies. Curr. Opin. Neurol. 29, 628\u2013634 (2016).","journal-title":"Curr. Opin. Neurol."},{"key":"e_1_3_3_63_2","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41593-018-0298-7","article-title":"A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology","volume":"22","author":"Fu H.","year":"2019","unstructured":"H. Fu ., A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology. Nat. Neurosci. 22, 47\u201356 (2019).","journal-title":"Nat. Neurosci."},{"key":"e_1_3_3_64_2","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1242\/jcs.199240","article-title":"Stress-specific differences in assembly and composition of stress granules and related foci","volume":"130","author":"Aulas A.","year":"2017","unstructured":"A. Aulas ., Stress-specific differences in assembly and composition of stress granules and related foci. J. Cell Sci. 130, 927\u2013937 (2017).","journal-title":"J. Cell Sci."},{"key":"e_1_3_3_65_2","doi-asserted-by":"crossref","first-page":"e1007737","DOI":"10.1371\/journal.pgen.1007737","article-title":"Filamentation of asparagine synthetase in Saccharomyces cerevisiae","volume":"14","author":"Zhang S.","year":"2018","unstructured":"S. Zhang, K. Ding, Q.-J. Shen, S. Zhao, J.-L. Liu, Filamentation of asparagine synthetase in Saccharomyces cerevisiae. PLoS Genet. 14, e1007737 (2018).","journal-title":"PLoS Genet."},{"key":"e_1_3_3_66_2","doi-asserted-by":"crossref","first-page":"E160","DOI":"10.3390\/biom8040160","article-title":"Regulation of cellular metabolism through phase separation of enzymes","volume":"8","author":"Prouteau M.","year":"2018","unstructured":"M. Prouteau, R. Loewith, Regulation of cellular metabolism through phase separation of enzymes. Biomolecules 8, E160 (2018).","journal-title":"Biomolecules"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1912897117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1912897117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T09:28:04Z","timestamp":1722331684000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1912897117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,1,21]]},"references-count":66,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2020,2,4]]}},"alternative-id":["10.1073\/pnas.1912897117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1912897117","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/692103","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.3410\/f.737247937.793587847","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,1,21]]},"assertion":[{"value":"2020-01-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}